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R Fischer

Publications and source records attributed to R Fischer.

At least 145 records · Page 8Linked to original sources
PubMed1999

Polycythemia vera megakaryocytes store and release lysozyme to a higher extent than megakaryocytes in secondary polycythemia (polyglobuly).

Lysozyme, a myelomonocytic marker not only exerts bacteriolytic, but also immunomodulatoric properties and was found to bind to the glycosaminoglycan serglycin, an important constituent of the extracellular matrix (ECM). Pathological serum lysozyme levels were described in chronic myeloproliferative disorders (CMPDs) and other hematological conditions. In this context it is remarkable that in polycythemia rubra vera (PV), characterized by a proliferation particularly of the megakaryo- and erythropoiesis, serum lysozyme levels behave independently of the numbers of myelomonocytic cells in peripheral blood. To elucidate whether megakaryopoiesis might be the source of the increased serum lysozyme, we performed an experimental study on isolated and enriched megakaryocytes derived from bone marrow of patients with PV. Findings were compared to a group of patients with reactive (smoker's) polyglobuly (PG). In confirmation of previous results, quantification of serum lysozyme levels showed a slight elevation in the cohort of PV patients which was not correlated with the leukocyte count. Applying an immunohistochemical assay we were able to demonstrate intracytoplasmic lysozyme storage in megakaryocytes. Moreover, performing the reverse hemolytic plaque assay (RHPA), a technique which enables detection of secreted proteins at the single cell level, we found that 54% of the PV, but only 3% of the PG megakaryocytes spontaneously secreted lysozyme. After rhIL-3 treatment the secretion of lysozyme remained unchanged in PV but increased to 14% in PG. These findings suggest that the extent of megakaryocytic lysozyme secretion might discriminate PV from reactive conditions. Although a direct involvement of lysozyme in the regulation of aberrant megakaryopoiesis in PV is not likely, the results of the present study point to the possibility that lysozyme could be involved in the interactions of PV megakaryocytes with ECM. Moreover, the response to rhIL-3 significantly discriminates PV megakaryocytes from megakaryocytes of the PG group.

Female↗
PubMed1999

Megakaryocyte induced fibroblast proliferation is enhanced by costimulation with IL-6/IL-3 and dependent on secretory and adhesion events.

Experimental data are in keeping with the finding that megakaryocytes isolated from normal human bone marrow may promote fibroblast growth. This effect can be significantly enhanced by interleukin (IL)-3. In this context it has been demonstrated that IL-3 induces the release of platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGFbeta1) from megakaryocytes, factors known to enhance fibroblast proliferation. The present in vitro study was performed to elucidate the action of several other cytokines which are able to influence the different steps of megakaryocyte maturation and function like stem cell factor (SCF), IL-6, and leukemia inhibitory factor (LIF) as well. Following an appropriate experimental design we were able to show that none of the mentioned cytokines enhanced megakaryocyte dependent fibroblast proliferation in the coculture assays. On the other hand, IL-6 in combination with IL-3 surpassed the IL-3 dependent action significantly. However, the combined IL-3/IL-6 effect was not explainable by an increased PDGF/TGF-beta secretion of the megakaryocytes. In transwell experiments the inhibition of cell-to-cell contact via tissue culture inserts generated a conspicuous impairment of fibroblast growth in the IL-3/IL-6 treated cocultures. This reversal surpassed even the effect on the untreated and IL-3 stimulated cocultures. Hence, a direct contact of both cell types probably inducing adhesion phenomenons and warranting a certain threshold of local PDGF/TGF-beta concentration is a prerequisite for the proliferative effect on fibroblasts in the costimulation experiments. These results are of special interest regarding the evolution of myelofibrosis in chronic myeloproliferative disorders (CMPDs) because (1) various progenitor cells including the megakaryocytic lineage are hypersensitive towards IL-3 and (2) an abnormal secretion of IL-6 is described for megakaryocytes in these disorders.

Cell Adhesion↗
PubMed1999

Characterization of nosocomial Serratia marcescens isolates: comparison of Fourier-transform infrared spectroscopy with pulsed-field gel electrophoresis of genomic DNA fragments and multilocus enzyme electrophoresis.

A total of 66 Serratia marcescens isolates from 46 patients was investigated by macrorestriction using XbaI followed by pulsed-field gel electrophoresis. 7 restriction fragment patterns attributable to more than one patient and 9 individual patterns were identified. The isolates were additionally characterized by multilocus enzyme electrophoresis and Fourier-transform infrared spectroscopy. The macrorestriction patterns and the multilocus enzyme electrophoresis patterns corresponded fairly well while the classifications derived from these methods were not completely congruent. The grouping achieved by Fourier-transform infrared spectroscopy on the basis of high (> 1000) and moderately high heterogeneity values (300) was consistent with the macrorestriction results. Grouping on a lower heterogeneity level did not contribute to further discrimination. In general, Fourier-transform infrared spectroscopy was less discriminatory than the two other methods, but easier to perform. Therefore, laboratories equipped with the necessary devices may use it to rapidly select bacterial isolates for macrorestriction or other well established characterization procedures.

Cross Infection↗
PubMed1999

Fusion imaging: combined visualization of 3D reconstructed coronary artery tree and 3D myocardial scintigraphic image in coronary artery disease.

BACKGROUND: In patients with coronary artery disease, coronary angiography is performed for assessment of epicardial coronary artery stenoses. In addition, myocardial scintigraphy is commonly used to evaluate regional myocardial perfusion. These two-dimensional (2D) imaging modalities are typically reviewed through a subjective, visual observation by a physician. Even though on the analysis of 2D display scintigraphic myocardial perfusion segments are arbitrarily assigned to three major coronary artery systems, the standard myocardial distribution territories of the coronary tree correspond only in 50-60% of patients. On the other hand, the mental integration of both 2D images of coronary angiography and myocardial scintigraphy does not allow an accurate assignment of particular myocardial perfusion regions to the corresponding vessels. To achieve an objective assignment of each vessel segment of the coronary artery tree to the corresponding myocardial regions, we have developed a 3D 'fusion image' technique and applied it to patients with coronary artery disease. The morphological data (coronary angiography) and perfusion data (myocardial scintigraphy) are displayed in a 3D format, and these two 3D data sets are merged into one 3D image. RESULTS: Seventy-eight patients with coronary artery disease were studied with this new 3D fusion technique. Of 162 significant coronary lesions, 120 (74%) showed good coincidence with regional myocardial perfusion abnormality on 3D fusion image. No regional myocardial perfusion abnormality was found in 44 (26%) lesions. Furthermore, the 3D fusion image revealed 24 ischemic myocardial regions that could not be related to angiographically significant coronary artery lesions. CONCLUSION: The results of this study demonstrate that our newly developed 3D fusion technique is useful for an accurate assignment of coronary vessel segments to the corresponding myocardial perfusion regions, and suggest that it may be helpful to improve the interpretative and decision-making process in the treatment of patients with coronary artery disease.

Aged↗
PubMed1999

Apoplastic and cytosolic expression of full-size antibodies and antibody fragments in Nicotiana tabacum.

We compared the expression of a functional recombinant TMV-specific full-size antibody (rAb29) in both the apoplast and cytosol of tobacco plants and a single chain antibody fragment (scFv29), derived from rAb29, was expressed in the cytosol. Cloned heavy and light chain cDNAs of full-size rAb29, which binds to TMV coat protein monomers, were integrated into the plant expression vector pSS. The full-size rAb29 was expressed in the cytosol and targeted to the apoplast by including the original murine antibody leader sequences. Levels of functional full-size rAb29 expression were high in the apoplast (up to 8.5 micrograms per gram leaf tissue), whereas cytosolic expression was low or at the ELISA detection limit. Sequences of the variable domains of rAb29 light and heavy chain were used to generate the single chain antibody of scFv29, which was expressed in the periplasmic space of E. coli and showed the same binding specificity as full-size rAb29. In addition, scFv29 was functionally expressed in the cytosol of tobacco plants and plant derived scFv29 maintained same binding specificity to TMV-coat protein monomers as rAb29.

Antibodies, Viral↗
PubMed1999

Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies.

We investigated the suitability of transformed rice cell lines as a system for the production of therapeutic recombinant antibodies. Expression constructs encoding a single-chain Fv fragment (scFvT84.66, specific for CEA, the carcinoembryonic antigen present on many human tumours) were introduced into rice tissue by particle bombardment. We compared antibody production levels when antibodies were either secreted to the apoplast or retained in the endoplasmic reticulum (ER) using a KDEL retention signal. Production levels were up to 14 times higher when antibodies were retained in the ER. Additionally, we compared construct sencoding different leader peptides (plant codon optimised murine immunoglobulin heavy and light chain leader peptides from mAb24) and carrying alternative 5' untranslated regions (the petunia chalcone synthase gene 5' UTR and the tobacco mosaic virus omega sequence). We observed no significant differences in antibody production levels among cell lines transformed with these constructs. The highest level of antibody production we measured was 3.8 micrograms g-1 callus (fresh weight). Immunological analysis of transgenic rice callus confirmed the presence of functional scFvT84.66. We discuss the potential merits of cell culture for the production of recombinant antibodies and other valuable macromolecules.

5' Untranslated Regions↗
PubMed1999

The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat.

With an organ transplant, hematopoietic donor cells are transferred to the recipient. To study the relevance of the resulting microchimerism for allograft acceptance, we analyzed a rat model of cyclosporine-induced tolerance for strongly incompatible heart allografts. Using a monoclonal antibody that detects a donor-specific CD45 allotype (RT7a), we selectively depleted donor leukocytes at different times after transplantation (days 0 or 18). Depletion was similarly effective at both times. However, only depletion on day 0 prevented tolerance induction and was associated with severe acute or chronic graft rejection. This indicates that passenger leukocytes have an essential immunomodulatory effect on the induction phase of allograft acceptance.

Animals↗
PubMed1999

Polycythemia vera megakaryocytes but not megakaryocytes from normal controls and patients with smokers polyglobuly spontaneously express IL-6 and IL-6R and secrete IL-6.

Polycythemia rubra vera (PV) represents a clonal hematological disorder defined by an abnormal expansion of erythroid precursors and megakaryopoiesis, in particular. Ample evidence has been provided that the IL-6/1L-6R complex may be responsible for the proliferation of normal and neoplastic megakaryocytes in vitro and this fact lead us to the hypothesis, that defects in the regulation of IL-6 synthesis take part in the pathogenesis of PV. The study was carried out to determine the IL-6 serum levels and the megakaryocytic IL-6 production in patients with PV and to compare these data with the situation in hematologically healthy donors as well as in patients suffering from spurious polycythemia--smokers polyglobuly (PG). For this purpose, IL-6 serum levels were measured by ELISA and the megakaryocytic production studied by immunohistochemistry, reverse hemolytic plaque assay (RHPA) together with reverse transcription/polymerase chain reaction (RT-PCR) in highly enriched megakaryocyte preparations. In additional experiments, the influence of IL-3 stimulation and the expression of IL-6R were tested. Serum levels of IL-6 did not differ between the three groups under study. In contrast, immunohistochemistry revealed a raised proportion of megakaryocytes expressing IL-6 in PV as compared to normal donors and patients suffering from PG. The percentage of megakaryocytes actively secreting this cytokine as detected by the RHPA was 20 times greater than in both the other groups. This phenomenon was further substantiated by the fact that IL-6 mRNA could only be shown in PV megakaryocyte preparations. The regulation of IL-6 secretion appears to be abnormal in PV. Whereas in the normal and in the PG group IL-3 stimulation exerts a marked increase in megakaryocytic IL-6 secretion, PV megakaryocytes responded with a paradoxical down-regulation of IL-6 synthesis combined with the loss of IL-6R. Our data describe for the first time an abnormally raised IL-6 production by PV megakaryocytes and point towards fundamental regulatory alterations of the IL-6 synthesis in this disease.

Bone Marrow↗
PubMed1999

Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF) - a clinicopathological study.

A clinicopathological follow-up study including sequential bone marrow biopsies was performed on 79 patients with idiopathic (primary) myelofibrosis (IMF) to characterize initial (prefibrotic) stages and to elucidate whether development of fibrosis was accompanied by corresponding clinical findings. For this purpose our cohort of patients was divided into two groups of which the first presented with the generally accepted signs and symptoms of IMF (group I; n = 60). Most patients of the second group (group II; n = 19) showed mild to moderate therapy-refractory anemia, minimal to slight splenomegaly and frequently thrombocytosis, but no bone marrow fibrosis at onset. Hematopoiesis was consistent with a striking hypercellularity in comparison to the age-related involution by adipose tissue, a conspicuous clustering and histotopographic dislocation of megakaryocytes, a neutrophil granulocytic proliferation and a reduction of erythropoietic islets with arrest of maturation. Most remarkable was the dysplastic cytology of megakaryocytes with a definitive deviation of differentiation resulting in bizarre forms. Follow-up examinations revealed that at later stages group II patients were not distinguishable from the first group with more advanced IMF. For this reason, these patients were regarded as presenting initial, prefibrotic IMF characterized by distinctive bone marrow features at the beginning. The prominent abnormalities of megakaryopoiesis together with the granulocytic proliferation were extremely helpful to differentiate prefibrotic IMF with accompanying thrombocythemia from essential thrombocythemia (ET). Dynamics of fiber progression were calculated by regarding increase in density per time. Speed of progression during the first year of observation proved to be significantly higher in group II patients with prefibrotic IMF in comparison to full-blown cases (group I). In conclusion, with respect to prospective clinical trials, diagnostic criteria for IMF should be re-evaluated by also taking initial, prefibrotic stages into account.

Anemia, Refractory↗
PubMed1999

Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis-a 2-year follow-up.

BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+-ATPase, necessary for the final step in gastric acid secretion. AIM: To assess safety and efficacy of oral pantoprazole (40 mg o.d.) used as a prophylaxis against relapse in patients with healed reflux oesophagitis during an open-label, 2-year study. METHODS: Outpatients (n=157) with healed stage II or III reflux oesophagitis (Savary-Miller classification) were enrolled into a long-term, multicentre maintenance study. Endoscopy was performed at entry into the study, after 12 and 24 months, or when disease-specific symptoms occurred on more than three consecutive days. Symptoms were assessed at 3-monthly intervals. Endoscopically confirmed relapses (at least stage I) were evaluated as treatment failures. RESULTS: Of the 178 adverse events, experienced by 88 (56%) patients (intention-to-treat population), 12 (7%) were assessed by the investigators as possibly related to the study medication. Median serum gastrin levels increased from a baseline of 46 ng/L to 90 ng/L, reaching a plateau after 9 months. For the intention-to-treat population the endoscopic remission rates after 12 and 24 months were 87% and 76%, respectively (Life-Table survival analysis, Kaplan-Meier). CONCLUSION: Pantoprazole 40 mg proved to be safe and efficacious during a 2-year prophylaxis treatment in patients with healed reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Maintenance therapy with pantoprazole 20 mg prevents relapse of reflux oesophagitis.

BACKGROUND: Proton pump inhibitors can be effective as maintenance therapy in reducing the relapse rate of reflux oesophagitis at a dose lower than that used for acute healing. PATIENTS AND METHODS: Patients (n=396, 18-88 years old) with healed reflux oesophagitis (grade II or III before healing) were included in this multinational, prospective, parallel-group, randomized double-blind study. They took oral pantoprazole 20 mg (n=203) or 40 mg (n=193), once daily for up to 12 months. Scheduled endoscopies were performed at entry, after 6 and 12 months, or when symptoms of at least moderate intensity were perceived on 3 consecutive days; symptoms were assessed every 3 months. The primary efficacy parameter was the time until endoscopically proven relapse of reflux oesophagitis occurred; the secondary parameters included tolerability, safety and time until symptomatic relapse occurred. RESULTS: Analysis was performed using the 'all-patients-treated' approach. Endoscopic relapse rates in the 20 mg group after 6 and 12 months were 16 and 29%, respectively; in the 40 mg group, they were 7 and 19%, respectively. Symptomatic relapse rates after 6 and 12 months were 14 and 21% in the 20 mg group and 10 and 17% in the 40 mg group, respectively. Pantoprazole 20 mg and 40 mg were well tolerated throughout the study; the type and frequency of adverse events reported were similar for both treatment groups. CONCLUSION: The 20 mg dose was proven to be 'at least equivalent' to the 40 mg dose with respect to endoscopic and symptomatic relapse. The 20 mg once daily dose represents an effective and safe maintenance regimen for the majority of patients with healed reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Expression and characterization of bispecific single-chain Fv fragments produced in transgenic plants.

We describe the expression of the bispecific antibody biscFv2429 in transgenic suspension culture cells and tobacco plants. biscFv2429 consists of two single-chain antibodies, scFv24 and scFv29, connected by the Trichoderma reesi cellobiohydrolase I linker. biscFv2429 binds two epitopes of tobacco mosaic virus (TMV): the scFv24 domain recognizes neotopes of intact virions, and the scFv29 domain recognizes a cryptotope of the TMV coat protein monomer. biscFv2429 was functionally expressed either in the cytosol (biscFv2429-cyt) or targeted to the apoplast using a murine leader peptide sequence (biscFv2429-apoplast). A third construct contained the C-terminal KDEL sequence for retention in the ER (biscFv2429-KDEL). Levels of cytoplasmic biscFv2429 expression levels were low. The highest levels of antibody expression were for apoplast-targeted biscFv2429-apoplast and ER-retained biscFv2429-KDEL that reached a maximum expression level of 1.65% total soluble protein in transgenic plants. Plant-expressed biscFv2429 retained both epitope specificities, and bispecificity and bivalency were confirmed by ELISA and surface plasmon resonance analysis. This study establishes plant cells as an expression system for bispecific single-chain antibodies for use in medical and biological applications.

Antibodies, Bispecific↗
PubMed1999

Treatment of women with an abnormal glucose challenge test (but a normal oral glucose tolerance test) decreases the prevalence of macrosomia.

Infant macrosomia is a serious medical concern. Pregnant women who do not meet the specific diagnosis for gestational diabetes may still have glucose-mediated macrosomia. In Santa Barbara County all pregnant women are screened for gestational diabetes at 24-28 weeks with a 50-g, 1-hr glucose challenge test (GCT). All patients who fail this test are placed on a standard euglycemic diet (40% carbohydrate, 20% protein, 40% fat) and perform home glucose monitoring of fasting and postprandial glucose levels. The objective of this study was to examine the effectiveness of this treatment program in decreasing infant macrosomia, maternal and infant morbidity, maternal complications, and operative delivery. We studied 103 women who had a positive GCT, but a negative 100-g, 3-hr oral glucose tolerance test (OGTT). The women were randomly assigned to either experimental or control groups with experimental women receiving dietary counseling and home glucose monitoring instruction (HBGM). HBGM diaries were reviewed weekly by clinic nurses. All women had hemoglobin A1c (HbA1c) tests at 28 and 32 weeks. Maternal and fetal charts were reviewed to determine delivery type and complications, indications for cesarean section (C-section), and infant gestational age, gender, Apgar scores, birth weight, morbidities, and congenital anomalies. Of the 103 women, 5 women required insulin treatment, 1 woman had an abortion, and 14 women were indeterminate regarding compliance or were control women who received diet counseling and HBGM. The results are based on 83 women--48 control and 35 experimental. There were no significant differences between the groups for age, parity, or weight at 28-30 weeks or 37 weeks to delivery, or HbA1c at 28 weeks. HbA1c was significantly higher in control women at 32 weeks. Birth weight expressed in grams or as a percentile specific for gender, ethnicity, and gestational age was significantly higher in control infants. Birth weight was significantly correlated with maternal intake weight, weight at 28-30 weeks, and weight at delivery and with HbA1c at 32 weeks' gestation. There were no significant differences between groups for maternal complications. Groups were significantly different for mode of delivery with experimental women having more induced vaginal deliveries but fewer repeat C-sections than control women. Groups were not different for primary C-sections. Women who fail the GCT, but not the OGTT and thus do not receive the diagnosis of GDM are still at risk for delivering a macrosomic infant and operative delivery. Our program of treatment for all women who fail the GCT improves outcome by reducing infant birth weight and the number of cesarean sections.

Adult↗
PubMed1999

Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation.

OBJECTIVE: Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr. METHODS: Outcome parameters were the SLE Disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR), a global damage index (DI) and required treatment. In 10 different European rheumatology centres, all SLE patients who were evaluated in the last 3 months of 1994, and who had been diagnosed with SLE at least 10 yr ago, were included in the study. RESULTS: It should be stressed that our results are confined to a patient cohort, defined by a disease duration of at least 10 yr, and who are still under clinical care at the different centres in Europe. These SLE patients still showed some disease activity, related to symptoms of the skin and musculoskeletal systems, next to the presence of renal involvement. A total of 72% of the patients needed treatment with prednisolone (</=7.5 mg). The cumulative damage was overall related to clinical features of the central nervous system (14%) and renal involvement (14%), next to deforming arthritis (14%), osteoporosis (15%) and hypertension (40%). The prevalences of obesity, Cushing appearance and diabetes are highly suggestive that the ongoing treatment and that in the past might have had an impact on the total sum of end-organ damage. CONCLUSIONS: After 10 yr, a high proportion of patients in our cohort continued to show evidence of active disease, defined by the SLEDAI as well as ECLAM. The DI was related to the involvement of the central nervous system, renal involvement and the presence of hypertension.

Adult↗
PubMed1999

Local effect of lung contusion on lung surfactant composition in multiple trauma patients.

OBJECTIVE: The aim of this study was to investigate the direct influence of lung contusion on pulmonary surfactant in multiple trauma patients. DESIGN: Prospective, nonrandomized study. SETTING: University hospital, trauma intensive care unit. PATIENTS: Eighteen multiple trauma patients with unilateral lung contusions and Injury Severity Scores >19 were studied prospectively. INTERVENTIONS: Bronchoalveolar lavage was performed daily until either day 7 or extubation. Samples from the side of lung contusion (n = 62) and the contralateral, uninjured side (n = 62) were obtained at the same time in 14 patients. Total phospholipids, total phospholipid classes, and surfactant apoprotein A were quantified. Additionally, surfactant function was measured with a pulsating bubble surfactometer in four patients. All data are presented as mean +/- SEM. Statistical analyses were performed using programs of SPSS for Windows 6.1.3 (SPSS Inc., Chicago, IL) (Student's t-test; p < .05). MEASUREMENTS AND MAIN RESULTS: Total phospholipids were significantly increased on the side of lung contusion (contusion side, 40+/-7 microg/mL; contralateral side, 21+/-3 microg/mL; p = .004). The percentage contents of phosphatidylcholine (contusion side, 87.1%+/-1.0%; contralateral side, 84.3%+/-1.0%; p = .04) and sphingomyelin (contusion side, 2.9%+/-0.3%; contralateral side, 1.9%+/-0.2%; p = .004) were significantly higher. In contrast, the percentage content of phosphatidylglycerol was significantly decreased (contusion side, 4.1%+/-0.1%; contralateral side, 6.9%+/-0.6%; p = .001). No alterations were found for the relative contents of phosphatidylethanolamine (contusion side, 2.4%+/-0.2%; contralateral side, 2.2%+/-0.2%; p = .47), phosphatidylinositol (contusion side, 3.5%+/-0.4%; contralateral side, 4.6%+/-0.5%; p = .06), and surfactant apoprotein A (contusion side, 7177+/-1404 ng/mL; contralateral side, 4513+/-787 ng/mL, p = .10). There was no statistical difference for minimal surface tension measured with the pulsating bubble surfactometer after 5 mins of oscillation (contusion side, 29.5+/-2.3 mN/m; contralateral side, 23.7+/-2.1 mN/m; p = .08). CONCLUSIONS: Direct damage of lung parenchyma by lung contusion alters the composition of surfactant. No additional changes in surfactant function were observed that would argue in favor of functional compensation.

Adult↗
PubMed1999

Problem-solving ability of inner-city children with and without in utero cocaine exposure.

To evaluate the problem-solving abilities of a cohort of inner-city cocaine-exposed children and controls, children were invited to play with the Goodman Lock Box, a large red and blue box with 10 compartments, each having a different lock and toy. Examiners, blinded to the children's group status, coded the children's activities during the 6.5-minute play period. Nineteen behaviors were collapsed into three outcomes: Aimless Actions, Competence, and Mental Organization. Groups' scores were compared with scores of the Goodman standardization sample of mixed socioeconomic status preschoolers. Seventy-three cocaine-exposed children and 82 controls were evaluated at age 3.5 years; of these, 58 cocaine-exposed and 63 controls were reevaluated at age 4.5 years. The groups' scores did not differ on any outcome at either time point (p > or = .22). However, both groups' Mental Organization scores were consistently lower than the Goodman group at each age (p < .01). This high-risk cohort may experience problems functioning in more complex environments such as the classroom.

Child, Preschool↗
PubMed1999

Nuclear movement in filamentous fungi.

One of the most striking features of eukaryotic cells is the organization of specific functions into organelles such as nuclei, mitochondria, chloroplasts, the endoplasmic reticulum, vacuoles, peroxisomes or the Golgi apparatus. These membrane-surrounded compartments are not synthesized de novo but are bequeathed to daughter cells during cell division. The successful transmittance of organelles to daughter cells requires the growth, division and separation of these compartments and involves a complex machinery consisting of cytoskeletal components, mechanochemical motor proteins and regulatory factors. Organelles such as nuclei, which are present in most cells in a single copy, must be precisely positioned prior to cytokinesis. In many eukaryotic cells the cleavage plane for cell division is defined by the location of the nucleus prior to mitosis. Nuclear positioning is thus absolutely crucial in the unequal cell divisions that occur during development and embryogenesis. Yeast and filamentous fungi are excellent organisms for the molecular analysis of nuclear migration because of their amenability to a broad variety of powerful analytical methods unavailable in higher eukaryotes. Filamentous fungi are especially attractive models because the longitudinally elongated cells grow by apical tip extension and the organelles are often required to migrate long distances. This review describes nuclear migration in filamentous fungi, the approaches used for and the results of its molecular analysis and the projection of the results to other organisms.

Aspergillus nidulans↗